1.1 Field of the Invention
In general, the invention relates to drug particles or drug delivery particles coated with a biodegradable or biocompatible material, such as a polymer, to control surface properties, drug diffusion rates and release rates. More particularly, the invention provides methods for preparing pharmaceutical compositions that are coated with ultrafine layers of organic polymeric coating materials applied through the non-aqueous, non-solvent technique of vapor deposition processes such as pulsed laser ablation. Among the many advantages of the disclosed methods are control of coating both the thickness and uniformity of the coating onto the surfaces of the selected particulate drug.
1.2 Description of Related Art
Currently, aqueous/solvent (wet/sol) techniques are used to produce polymeric coatings onto particulate materials (Zeng, 1995). Poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and their copolymers poly(lactic-co-glycolic acid) (PLGA) have been used to create microspheres that are currently being researched for pulmonary drug delivery of several drugs, but common solvent-evaporation techniques produce low encapsulation efficiencies (1–10%) and complicated processing (Talton, 1999). Unfortunately, the present methods of applying these coatings onto particles for pulmonary drug delivery have not yet effectively achieved particles in the micron size range.
Dry-powder inhalers (DPI) are used to deliver various drugs to the lungs for either localized or systemic delivery (Zeng, 1995). Although the current drug delivery systems are moderately efficient for pulmonary drug administration, they are limited by potential problems with pulmonary deposition characteristics as well as the release-rate kinetics of the drug after inhalation (Hochhaus, 1997).
Nanocapsule and microsphere formulations that are well known in the pharmaceutical arts have been typically inefficient in delivering drugs to the pulmonary surface via inhalation, and control of the particle size and coating thicknesses have been problematic. Similar shortcomings have been encountered using liposomal formulations to coat drug particles.
1.3 Deficiencies in the Prior Art
As noted above, the prior art methods are lacking in many respects for the preparation of coated drug particles that are optimized for aerosol and inhalation therapies. Only limited reports have used pulsed laser deposition to deposit polymeric nano-particle coatings on flat surfaces (Hansen, 1988; Blanchet, 1993; Li, 1998; Suzuki, 1998), and none have reported coatings on particles. Likewise, prior deposition methods have been largely unable to reproducibly prepare ultrafine-coated drug properties with sufficient pharmaceutical activity to make them useful for aerosol delivery of drugs to the pulmonary surfaces of an animal lung. The most severe limitations of the prior art methods include low encapsulation efficiency, long processing times, and porosity from solvent evaporation (Talton, 1999).
Therefore, what is needed are improved methods for preparing ultrafine coated drug particles that do not suffer these limitations, and that are useful in preparing pharmaceutical formulations with superior drug delivery and efficacy properties. Particularly lacking are methods for the preparation of medicaments that comprise coated drug particles of a size and functionality that are useful for aerosol or other pulmonary delivery.